Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: LSR Standard Operating Procedure QAU/020 and QAU/040
Deviations:
not applicable
GLP compliance:
no
Test type:
concentration x time method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
Sponsor's identification
Description
Batch number
Date received
Storage conditions
PCMX
cream coloured, crystalline solid
285/13847
27 September 2001
room temperature, in the dark
Specific details on test material used for the study:
The test compound as received was micronised before use.
Test atmospheres were generated using a Wright dust feed mechanism (L, Adams Limited, London, England) mounted on the top of the chamber. Dry oil-free compressed air was passed through the apparatus at a pressure of 10 psi , givi ng an air-flow of ca. 18 L/min

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Young adult albino rats of the CD strain (remote Sprague-Dawley origin) , supplied by Charles River (U.K. ) Limited, were about 6 - 11 weeks old on arrival and were within the bodyweight range 180 - 198 g for males and 198 - 215 g for female rats. The animals had been bred under barriered conditions and travel led from the supplier to the animal-holding room in sealed boxes with filter protected airvents. The albino rat was selected for this study as the standard laboratory species for use in acute toxicity tests, The strain has been used for toxicological purposes since its establishment under S.P.F. conditions in 1955. There is extensive knowledge of the biology of the individual animal .
The animals were housed in high density polypropylene cages, measuring 56 x 38 x 18 cm, with stainless steel grid floors and tops (North Kent Plastics Limited), The grid floor ensured rapid removal of waste material to undertrays which were cleaned as necessary. In the preliminary study each cage contained two animals of the same sex. In the main study, a minimum floor area of 250 cm 2 per rat was provided by housing five animals, of the same sex and dosage group, in each cage. Mobile tubular steel racks each held up to 21 suspended cages.
Each room within the l imited-access building has been assigned to one species alone. Al l rooms were kept at slight positive pressure relative to the outside and each had its own filtered air supply giving approximately 17 complete air changes per hour without recirculation. The maximum and minimum temperatures of the previous 24-hour period and the relative humidity were recorded at the beginning of each working day, The target temperatures and humidity values for the animal room were 2 IC (acceptable limits 18 0 - and 55% R.H. (acceptable l imits 40% - 70% R.H. ) respectively.
Electric time-switches regulated a lighting cycle of 12 hours of artificial light per day. A stand-by generator was available to maintain the electricity supply in the event of a mains power failure. All personnel entering the building changed into clean protective clothing and wore an additional gown, alternative footwear, gloves and face mask to service animal -holding areas.
A commercially-available complete pelleted rodent diet (Spratt's Laboratory Diet No. 1 from K and K Greeff Ltd. , Croydon, London) was fed without restriction, except for the removal of food approximately 18 hours before the test substance was administered.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
ca. 6.29 other: mg/L
Geometric standard deviation (GSD):
>= 2.8 - <= 3.1
Remark on MMAD/GSD:
See study
Details on inhalation exposure:
Particle size distribution
The particle size distribution was measured twice per hour during the exposure period.
The aerosol was characterised using a cascade impactor (Model MKIIa, from C. F, Casella and Company Limited, London) which was located into a vacant animal exposure. The particle size distribution (from which the median EAD was derived) was detemined using the ECD (Effective Cut-off Diameter) method of bulk estimation, the mass recovered at each stage being detemined by the weight gain of the sampling discs,
All weighing was perfomed using an electronic balance (Model 2006 MP6, Sartorius Instruments Limited, Surrey) and recorded to the nearest 0, 1 milligram.
A clean glass sampling disc was used as a check weight for each series of weighings.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Remarks on duration:
A single four-hour period. Signs of reaction to treatment were recorded during a subsequent 14day period of observation, All animals were sacrificed on Day 15 and subjected to a detailed necropsy.
Concentrations:
The acute inhalation toxicity of 4-chl oro-3.5-xy1en01 , hereafter referred to as PCMX, was investigated i n a group of five male and five female rats exposed by snout only to the maximum practicable concentration of 6.29 mg/L of PCMX, for a single four-hour period. Signs of reaction to treatment were recorded during a subsequent 14day period of observation, All animals were sacrificed on Day 15 and subjected to a detailed necropsy.
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs,organ weights, body weight

Results and discussion

Preliminary study:
A dose range-finding test was performed using two males and two female rats.
Effect levels
Sex:
male/female
Dose descriptor:
other: dose-range finding
Effect level:
7.9 mg/L air
Based on:
test mat.
Remarks on result:
other: No observed deaths
Mortality:
0
Clinical signs:
0
Body weight:
n/a
Gross pathology:
0
Other findings:
Because no death occurred as a result of treatment, the low toxicity of PCMX was demonstrated by administeri ng the maximum practicable air concentration to a single group of five males and five females.

Applicant's summary and conclusion

Interpretation of results:
other: Meets standards of the day, LSR SOP's
Conclusions:
Under the conditions of this study, the acute median lethal concentration for four hour exposure (LC four-hour) to PCMX was above 6.29 mg/ z
Executive summary:

A total PCMX aerosol concentration of 6.29 mg/L was achieved as compared with a nominal value of 9.4 mg/L calculated from materials balance. Measurements of particle size indicated that cae 24% by weight of the suspended PCMX aerosol consisted of particles with equivalent aerodynamic diameters less than 5 um, which could be considered respirable to the rat.